The mammalian body is composed of several lineage-committed cells that give rise to the many tissues of a mammalian body. Despite the diversity of the nature, morphology, characteristics and function of such lineage committed cells, it is presently believed that most, if not all, the lineage committed cells are derived from various stem cells that give rise to one or more of the lineage committed cells of the mammalian body. Such stem cells constitute only a small percentage of the total number of cells present in the body and can vary depending up their relative commitment to a particular cell type. In addition, it is not known what markers associated with lineage committed cells are also present on stem cells. One marker which has been indicated as present on stem cells, CD34, is also found on a significant number of lineage committed progenitors. In particular, B-cells (CD19+) and myeloid cells (CD33+) make up 80-90% of the CD34+ population. Moreover, a combination of CD3, 8, 10, 15, 19, 20, and 33 will be present on >90% of all CD34+ cells. Therefore, in view of the small proportion of the total number of cells in the bone marrow which are stem cells, the uncertainty of the markers associated with the stem cell as distinct from more differentiated cells, and the general inability to biologically assay for human stem cells, the identification and purification of stem cells has been elusive.
Endothelial cells are a cellular organizational unit of vascular structures. Their linear commitment, expansion, and assembly into blood vessels are required for organogenesis during embryonic development. During angiogenesis, endothelial cells in existing vessels are activated by angiogenesis factors, such as TGF, FGF, and VEGF. New vessels are formed through cell proliferation and migration, and the elongation and branching of existing vessels.
Identification of a readily available source of stem cells that can give rise to endothelial cells is needed. The need is particularly acute for stem cells from adult sources, in light of restrictions recently placed on the use of federal funding for embryonic stem cell research. Possession of such stem cells will allow for identification of growth factors associated with endothelial cell regeneration. In addition, there may be as yet undiscovered growth factors or other biological factors (e.g., transcription factors) associated with the early steps of dedication of the stem cell to an endothelial cell lineage, the prevention of such dedication, and the negative control of stem cell proliferation. The availability of stem cells would be extremely useful in vascular transplantation, tissue engineering, regulation of angiogenesis, vasculogenesis, and the prevention thereof. The stem cells and their progeny can find use in the treatment of myocardial damage and repair. Such stem cells also could be used to introduce a gene into a subject as part of a gene therapy regimen.